Cytochrome P450db; K+ channel

1. The effect of quinidine on the fast-activating, fast-inactivating potassium current (IK(f] in acutely dissociated melanotrophs of the adult rat pituitary was examined. Macroscopic currents were measured by use of the whole-cell configuration of the patch clamp technique. 2. Bath application of quinidine caused a dose-dependent reduction of the peak amplitude of IK(f). The Kd for blockade of IK(f) at 0 mV was estimated to be 41 +/- 5.6 microM. 3. Quinidine elicited a dose-dependent increase of the rate of the decay of IK(f) and this effect was enhanced by membrane depolarization. The possibility that this phenomenon reflects an open channel blocking reaction is discussed. 4. Quinidine also caused a 5 mV hyperpolarizing shift of the steady-state inactivation curve and increased the half-time for recovery from inactivation. Quinidine did not affect the onset of inactivation measured at -30 mV. 5. Internal quinidine did not appear substantially to affect either the peak amplitude or kinetics of IK(f). 6. A study of some structural analogues showed that hydroquinidine and quinacrine had effects similar to those of quinidine. The effect of quinacrine on the amplitude and kinetics of IK(f) was also pH-dependent. Cinchonine, which bears a close structural resemblance to quinidine, was much less effective as a blocker of IK(f).[1]

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Multidrug resistance (MDR) is one of important issues to cause the chemotherapy failure against cancers including gynecological malignancies. Despite some MDR reversal evidences of natural compounds including quinidine and cinchonine, there are no reports on MDR reversal activity of hydrocinchonine with its analogues quinidine and cinchonine especially in uterine sarcoma cells. Thus, in the current study, we comparatively investigated the potent efficacy of hydrocinchonine and its analogues quinidine and cinchonine as MDR-reversal agents for combined therapy with antitumor agent paclitaxel (TAX). Hydrocinchonine, cinchonine, and quinidine significantly increased the cytotoxicity of TAX in P-glycoprotein (gp)-positive MES-SA/DX5, but not in the P-gp-negative MES-SA cells at nontoxic concentrations by 3-(4,5-dimethylthiazol-2-yl)-2,5--diphenyltetrazolium bromide (MTT) assay. Rhodamine assay also revealed that hydrocinchonine, cinchonine, and quinidine effectively enhanced the accumulation of a P-gp substrate, rhodamine in TAX-treated MES-SA/DX5 cells compared with TAX-treated control. In addition, hydrocinchonine, cinchonine, and quinidine effectively cleaved poly (ADP-ribose) polymerase (PARP), activated caspase-3, and downregulated P-gp expression as well as increased sub-G1 apoptotic portion in TAX-treated MES-SA/DX5 cells. Taken together, hydrocinchonine exerted MDR reversal activity and synergistic apoptotic effect with TAX in MES-SA/DX5 cells almost comparable with quinidine and cinchonine as a potent MDR-reversal and combined therapy agent with TAX.[4]

Amphetamine is metabolized by cytochrome P-450 (P450) to p-hydroxyamphetamine and phenylacetone in mammalian species. P450 metabolism is affected by genetic polymorphisms and by xenobiotic interactions in an isozyme-specific fashion. Little is known concerning the isozyme selectivity of amphetamine metabolism. Quinidine selectively inhibits the debrisoquine-specific isozyme (P450db) which displays genetic polymorphism in humans and rats. We now report the effect of quinidine on the metabolism of amphetamine to p-hydroxyamphetamine in vivo. At 0 h male Lewis rats received (po): no treatment (I), 80 mg quinidine/kg in 50% ethanol (II), or 50% ethanol (III), followed at 2 h by 15 mg d-amphetamine sulfate/kg (po). Urine specimens were collected and pooled at 0, 24, and 48 h. Amphetamine and p-hydroxyamphetamine concentrations were determined using a new GC/MS method for simultaneous quantitation. The ethanol vehicle-control (III) had no significant effect on amphetamine metabolism. Quinidine pretreatment (II) resulted in a significant decrease in the excretion of p-hydroxyamphetamine at 24 and 48 h to 7.2 and 24.1% of the vehicle-control levels, respectively, accompanied by a significant increase in amphetamine excretion between 24 and 48 h to 542% of the control. These data show that quinidine inhibits in vivo metabolism of amphetamine in rats and suggest that amphetamine metabolism may, in part, be mediated by an isozyme of P450 which displays genetic polymorphism. The inhibition of amphetamine metabolism results in an increased ratio of parent drug to metabolite concentration (metabolic ratio) in the urine, which mimics the effect of genetic polymorphisms[3].

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This study aimed to investigate the effects of dextromethorphan (DM) or dextromethorphan/quinidine (DM/Q) against pentylenetetrazole (PTZ)- induced seizure threshold in mice and the probable involvement of N-methyl d-aspartate (NMDA), sigma-1 and serotonin 1A (5-HT1A) receptors.
Results: DM (25 and 50 mg/kg) significantly increased PTZ- induced seizure threshold. DM/Q at doses of 10/20 and 25/20 mg/kg had anticonvulsant effect, while at a dose of 50/20 mg/kg attenuated anticonvulsant effect of DM 50 mg/kg. Ketamine (5 mg/kg) or WAY-100635 (1 mg/kg) potentiated, while BD-1047 (2.5 and 5 mg/kg) attenuated the anticonvulsant effect of DM/Q 10/20 mg/kg.
Conclusion: The results of present study demonstrate that combination with quinidine potentiates the anticonvulsant effect of DM at lower doses, while attenuates it at higher dose. Meanwhile, the effects of DM/Q on seizure activity likely involve an interaction with NMDA, the sigma-1 or the 5-HT1A receptor which may be secondary to the elevation of DM levels.[5]

Cytotoxicity assay [4]
Cell Types: MES-SA and MESSA/DX5 Cell
Tested Concentrations: 10 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: demonstrated cytotoxicity to MES-SA cells and can induce cytotoxicity [4]. MES-SA cells in a concentration-dependent manner.

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Apoptosis analysis [4]
Cell Types: MES-SA and MESSA/DX5 Cell
Tested Concentrations: 10 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: The content of sub-G1 DNA in the apoptotic part induced by paclitaxel increased, while paclitaxel did not affect sub-G1 DNA Influence the contents to undergo apoptosis.

Animal/Disease Models: NMRI strain male mice (age 5-6 weeks, weight 25-30 g) [5 doses: 10, 20, 30 mg/kg
Route of Administration: intraperitoneal (ip) injection; 10, 20 and 30 mg/kg;
Experimental Results: vs. The 30 mg/kg dose increased the threshold dose for tonic hindlimb extension attacks compared to the saline-treated control group (p<0.05).

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NMRI male mice (25-30 g) received quinidine (10, 20, and 30 mg/kg), dextromethorphan (DM) (5, 10, 25, and 50 mg/kg) or dextromethorphan/quinidine (DM/Q) (10/20, 25/20, and 50/20 mg/kg), 30 min before the infusion of PTZ. ketamine (1 and 5 mg/kg), BD-1047 (2.5 and 5 mg/kg) or WAY-100635 (0.5 and 1 mg/kg) were administrated as pre-treatment 30 min before the selected dose of DM/Q. Seizures were induced by intravenous PTZ infusion. All data were presented as means ± S.E.M. One-way ANOVA test was used to determine statistical significance (p < 0.05).[5]

Absorption, Distribution and Excretion
Quinidine sulfate has an absolute bioavailability of approximately 70%, ranging from 45% to 100%. This bioavailability is not entirely due to first-pass metabolism in the liver. In contrast, quinidine gluconate has an absolute bioavailability of 70% to 80%, and the bioavailability of quinidine in gluconate is 1.03 relative to quinidine sulfate. The time to peak concentration (tmax) of quinidine sulfate extended-release tablets is approximately 6 hours, while that of quinidine gluconate is 3 to 5 hours. When taken with food, the peak plasma concentration of immediate-release quinidine sulfate is delayed by approximately 1 hour. Furthermore, drinking grapefruit juice may reduce the absorption rate of quinidine. Quinidine is primarily eliminated through renal excretion (15% to 40% of total clearance) and hepatic biotransformation into various metabolites (60% to 85% of total clearance). When urine pH is below 7, 20% of quinidine is present in the urine unchanged. However, this percentage decreases to about 5% as urine pH increases. Renal clearance of quinidine involves glomerular filtration and active tubular secretion, and is regulated by pH-dependent tubular reabsorption. The volume of distribution of quinidine is 2–3 L/kg in healthy young adults, 0.5 L/kg in patients with congestive heart failure, and 3–5 L/kg in patients with cirrhosis. The clearance rate of quinidine in adults ranges from 3 to 5 mL/min/kg. In pediatric patients, the clearance rate of quinidine may be two to three times that of adults. The volume of distribution of quinidine in healthy young adults is 2 to 3 L/kg, but it can decrease to 0.5 L/kg in patients with congestive heart failure, and increase to 3 to 5 L/kg in patients with cirrhosis. When quinidine concentrations are 2 to 5 mg/L (6.5 to 16.2 μmol/L), plasma protein binding (primarily to α1-acid glycoprotein and albumin) is 80% to 88% in adults and older children, but lower in pregnant women and as low as 50% to 70% in infants and newborns. Because stress responses lead to elevated α1-glycoprotein levels, serum total quinidine levels may be significantly elevated in cases such as acute myocardial infarction, even if serum free (active) drug levels may remain normal. Protein binding is also elevated in chronic renal failure, but rapidly decreases to near or below normal levels when heparin is used for hemodialysis. ...After oral administration, it is essentially completely absorbed; the maximum effect occurs within 1–3 hours and lasts for 6–8 hours. Repeated administration within this time interval may result in significant fluctuations in plasma concentrations. ...Intramuscular injection...gluconate reaches peak effect within 30–90 minutes. All administered compounds are excreted by the kidneys, with approximately 10-50% appearing in the urine unchanged as quinidine within 24 hours. The bioavailability of oral quinidine is 70% to 80%, but varies by individual and formulation. Sulfates are rapidly absorbed within 60 to 90 minutes. Polygalacturonates reach peak quinidine concentrations within 5 to 6 hours; gluconate absorption in the gastrointestinal tract falls between these two (peak absorption at 3 to 4 hours). For more complete data on the absorption, distribution, and excretion of quinidines (14 in total), please visit the HSDB records page. Approximately 90% of quinidine in plasma is bound to plasma proteins (α/acid glycoproteins and albumin). The drug enters red blood cells and binds to hemoglobin; at steady state, the concentrations of quinidine in plasma and red blood cells are approximately equal. Quinidine accumulates rapidly in most tissues except the brain, with a volume of distribution of 2-3 liters/kg. Quinidine metabolites and a portion of the original drug (20%) are excreted in the urine; the elimination half-life is approximately 6 hours. The main elimination pathways of quinidine are hepatic metabolism and renal excretion. Enterohepatic circulation does not significantly alter absorption kinetics, which is reflected in plasma drug concentrations. Four hours after administration of the extended-release capsules (250 mg quinidine sulfate), the peak plasma concentration of quinidine was 0.29 μg/mL, which steadily decreased over the next 8 hours; while after administration of the extended-release tablets (300 mg quinidine sulfate), plasma concentrations remained relatively stable over 2–10 hours. Plasma concentrations of capsules were higher than those of tablets in the later stages. Compared to tablets, the bioavailability of quinidine in capsules was 184% over 12 hours. The mean plasma concentrations of quinidine were significantly higher at 3, 4, 6, 8, and 10 hours after administration of capsules than after administration of tablets. For more complete data on absorption, distribution, and excretion of quinidine sulfate (24 items), please visit the HSDB records page.

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Metabolism/Metabolites
Quinidine is primarily metabolized in the liver by cytochrome P450 enzymes, particularly CYP3A4. The major metabolite of quinidine is 3-hydroxyquinidine, which has a larger volume of distribution than quinidine and an elimination half-life of approximately 12 hours. Non-clinical and clinical studies have shown that the antiarrhythmic activity of 3-hydroxyquinidine is approximately half that of quinidine; therefore, this metabolite is responsible for some of the adverse reactions observed with long-term quinidine use. Lactate conjugates of quinidine and its 3-hydroxy metabolite were detected in a patient who attempted suicide by overdose of quinidine. Quinidine is primarily metabolized in the liver, mainly through hydroxylation to produce 3-hydroxyquinidine and 2-quinidineone. Some metabolites possess antiarrhythmic activity. Approximately 10-50% of the dose is excreted unchanged in the urine within 24 hours (possibly through glomerular filtration). Quinidine metabolites include 3-hydroxyquinidine N-oxide, 2'-oxoquinidine ketone, desmethylquinidine, and quinidine N-oxide. While there is considerable inter-individual variability in metabolism, at least in cases of quinidine-induced torsades de pointes, the metabolites do not appear to be involved in the formation of the arrhythmia. Quinidine undergoes extensive oxidative metabolism in the liver…one of the metabolites, 3-hydroxyquinidine, has an almost equivalent ability to block cardiac sodium channels or prolong action potentials as quinidine. Most quinidine is cleared from the liver by the action of cytochrome P450 IIIA. Quinidine is metabolized in humans as 2'-hydroxyquinidine. /quinidine; from table/ Most urinary metabolites are hydroxylated at only one site, either on the quinoline ring or the quinine ring; small amounts of dihydroxy compounds have also been found. The metabolic proportions and pathways of quinidine appear to vary from patient to patient. Quinidine is primarily metabolized in the liver, via hydroxylation to produce 3-hydroxyquinidine and 2-quinidineone. These metabolites may be pharmacologically active. Approximately 10-50% of the dose is excreted unchanged in the urine within 24 hours (possibly through glomerular filtration). Quinidine's known metabolites include 3-hydroxyquinidine and quinidine-N-oxide. Biological Half-Life: The elimination half-life of quinidine in adults is 6-8 hours, and in pediatric patients it is 3-4 hours. The plasma half-life of quinidine in healthy individuals is typically 6-8 hours, but can be 3-16 hours or longer. In a study of patients with Plasmodium falciparum malaria, the mean elimination half-life was 12.8 hours (range: 6.6-24.8 hours). After intravenous administration, the plasma half-life is typically approximately 7 hours, but is prolonged in patients with chronic liver disease. Quinidine's elimination half-life in healthy individuals ranges from 4 to 10 hours, with a typical average of 6 to 7 hours. The half-life is significantly prolonged in older adults, even if they appear healthy. /Quinidine/ ...excreted in urine; elimination half-life is approximately 6 hours. The plasma half-life of quinidine in healthy individuals is typically 6–8 hours, but can be 3–16 hours or longer. In a study of patients with Plasmodium falciparum malaria, the average elimination half-life of the drug was 12.8 hours (range: 6.6–24.8 hours).

Toxicity Summary
Identification: Quinidine is a Class IA antiarrhythmic drug. Source: Quinidine is the d-isomer of quinine. Quinidine is an alkaloid that may be derived from various cinchona trees. Cinchona bark contains 0.25% to 3.0% quinidine. Quinidine can also be prepared from quinine. Quinidine is a white powder or crystal, odorless, and bitter. Quinidine sulfate is a colorless crystal, odorless, and bitter. Quinidine gluconate is a white powder, odorless, and bitter. Quinidine polygalacturonic acid is a powder. Quinidine sulfate is a white powder or odorless crystal, bitter. Indications: Description: Ventricular premature beats and ventricular tachycardia; supraventricular arrhythmias; maintenance of sinus rhythm after cardioversion of atrial fibrillation or atrial flutter. Human Exposure: Major Risks and Target Organs: Cardiotoxicity is the major risk of quinidine poisoning. Quinidine may induce central nervous system symptoms. Clinical Overview: Symptoms of poisoning usually appear within 2–4 hours after ingestion, but the delay may vary depending on the quinidine salt and formulation. Symptoms may include cardiac arrhythmias (especially in patients with underlying cardiovascular disease), neurotoxicity, and respiratory depression. Diagnosis: Cardiac disturbances: circulatory arrest, shock, conduction disturbances, ventricular arrhythmias, ECG changes; neurological symptoms: tinnitus, somnolence, syncope, coma, seizures, delirium; respiratory depression. Quinidine concentration may be helpful in diagnosis but not in clinical treatment. Contraindications: Hypersensitivity or idiosyncratic reaction to cinchona alkaloids; atrioventricular block or complete atrioventricular block; intraventricular block; loss of atrial activity; digitalis poisoning; myasthenia gravis and torsades de pointes. Precautions include: congestive heart failure, hypotension, kidney disease, liver failure; concurrent use of other antiarrhythmic drugs; elderly and lactating women. Route of Administration: Oral: Oral absorption is the most common cause of poisoning. Parenteral administration: Poisoning after intravenous administration is rare, but there have been reports of poisoning in patients receiving intravenous quinidine for arrhythmia. Absorption routes: Oral: Quinidine is almost completely absorbed via the gastrointestinal tract. However, due to the first-pass effect in the liver, its absolute bioavailability is approximately 70% to 80% of the ingested dose and may vary depending on the patient and formulation. The peak plasma concentration time for quinidine sulfate is 1 to 3 hours, for quinidine gluconate it is 3 to 6 hours, and for quinidine polygalacturonic acid it is approximately 6 hours. Sustained-release quinidine can be absorbed continuously over 8 to 12 hours. Parenteral administration: Absorption of quinidine after intramuscular injection can be unstable and unpredictable; the administered dose may not be completely absorbed, possibly due to drug precipitation at the injection site. Other studies have shown no difference in absorption rates between intramuscular and oral quinidine. Drug distribution: Oral: Protein binding: Approximately 70% to 80% of the drug is bound to plasma proteins. Plasma protein binding is reduced in patients with chronic liver disease. Tissues: Quinidine concentrations in the liver are 10 to 30 times higher than in plasma. Quinidine levels in skeletal muscle, cardiac muscle, brain, and other tissues fall between these levels. The erythrocyte-plasma partition ratio is 0.82. Biological half-life determined by exposure route: Elimination half-life: The half-life is approximately 6 to 7 hours. The half-life is prolonged in chronic liver disease and in older adults. Congestive heart failure or renal failure does not appear to alter its half-life. Metabolism: 50% to 90% of quinidine is metabolized in the liver to hydroxylated products. Metabolites include 3-hydroxyquinidine, 2-oxoquinidine, O-demethylquinidine, and quinidine-N-oxide. The major metabolite is 3-hydroxyquinidine, which has similar effects to quinidine and may partially explain the observed antiarrhythmic effects. The elimination kinetics of hydroxyquinidine appear to be similar to those of quinidine. Elimination determined by exposure route: Kidneys: The amount of drug excreted unchanged in urine varies considerably, but is approximately 17% of the administered dose. After administration of quinidine, up to 50% of the dose (net drug + metabolites) is excreted in the urine within 24 hours. Renal excretion depends on urine pH, and the amount excreted is inversely proportional to urine pH. Renal insufficiency and congestive heart failure reduce excretion. Liver: 50% to 90% of the quinidine dose is metabolized in the liver. Bile: Approximately 1% to 3% of quinidine is excreted in the feces via bile. Breast milk: Quinidine is secreted into breast milk. Mechanism of action and toxicology: Quinidine reduces myocardial permeability to electrolytes (membrane stabilizer) and is a systemic cardiac depressant. It has a negative inotropic effect, inhibiting spontaneous diastolic depolarization, slowing conduction velocity, prolonging the effective refractory period, and increasing the electrical threshold. This leads to decreased myocardial contractility, impaired conduction (atrioventricular and intraventricular conduction), and decreased excitability, but may be accompanied by anomalous reentry mechanisms. Quinidine has anticholinergic and peripheral vasodilatory effects. The following progressive changes were observed in experimental studies: Electrocardiogram: bradycardia, prolonged PR interval, prolonged QT interval, widened QRS complex, and the appearance of ventricular voluntary rhythms, eventually progressing to ventricular arrest. Sometimes, the terminal event is ventricular fibrillation. Blood pressure gradually decreases. Blood pressure drops significantly when QRS widening occurs, and approaches zero when slow ventricular voluntary rhythms occur. Electrolyte abnormalities: decreased plasma potassium, sodium, and magnesium concentrations, and acidosis. Electrolytes: hypokalemia may occur, possibly related to intracellular potassium transport through direct effects on cell membrane permeability. Neurological symptoms: syncope and seizures may represent direct toxicity to the central nervous system or may be related to cerebral ischemia caused by circulatory or respiratory failure. Pharmacodynamics: Quinidine can slow the firing rate of normal and ectopic rhythmic pacemakers; increase the threshold for electrically induced arrhythmias; prevent ventricular arrhythmias; and prevent or terminate vortex fibrillation. Teratogenicity: Quinidine has been shown to cause minor cranial nerve damage in fetuses, even at doses far exceeding those required for treating arrhythmias. Drug Interactions: Several drug interactions have been reported. Quinidine has a synergistic effect with warfarin (lowering prothrombin levels). Quinidine can enhance the effects of non-depolarizing and depolarizing neuromuscular blocking agents. When used in combination with other antiarrhythmic drugs, quinidine can enhance the cardiodepressant effects of these drugs. Amiodarone can increase blood quinidine concentrations. Rifampin, anticonvulsants, nifedipine, and acetazolamide can decrease quinidine concentrations. Antacids, cimetidine, verapamil, and amiodarone can increase quinidine concentrations; terfenadine, astemizole, as well as thiazide diuretics and loop diuretics increase the risk of quinidine toxicity. Quinidine can increase plasma concentrations of propafenone and digoxin. Major Adverse Reactions: Several adverse reactions have been reported during quinidine treatment. Cardiovascular system: Hypotension; syncope following intravenous administration; arrhythmic effects: torsades de pointes; ECG: widened QRS interval; prolonged PR and QT intervals. Central nervous system: Quinidine poisoning: headache, fever, visual disturbances, mydriasis, tinnitus, nausea, vomiting, and rash. Gastrointestinal tract: Nausea, vomiting, diarrhea, and colic have been reported. Liver: Granulomatous hepatitis or hepatitis with centrilobular necrosis. Skin: Drug fever and photosensitive rash may occur. Hematologic system: Thrombocytopenia (immune reaction) has been reported. Clinical manifestations: Acute poisoning: Ingestion: The severity of quinidine poisoning is related to cardiotoxicity. Symptoms usually appear within 2 to 4 hours and may include: Cardiovascular symptoms: hypotension, cardiogenic shock, cardiac arrest. Electrocardiogram (ECG) may show: decreased T waves; prolonged QT and QRS intervals; atrioventricular block; ventricular arrhythmias (torsades de pointes). Neurological symptoms: tinnitus, drowsiness, syncope, coma, seizures, blurred vision, and diplopia. Respiratory symptoms: hypoventilation and apnea. Cardiotoxicity may be exacerbated if other cardiotoxic drugs (antiarrhythmic drugs, tricyclic antidepressants) are ingested concurrently. Parenteral exposure: Symptoms appear more quickly after intravenous administration. Chronic poisoning: Ingestion: The most relevant symptoms of chronic poisoning are: ECG abnormalities; syncope due to ventricular arrhythmias (torsades de pointes) and cinchona poisoning; gastrointestinal disturbances. Course, prognosis, and cause of death: The typical course of quinidine poisoning is dominated by cardiovascular disturbances, usually appearing within the first 2 to 4 hours, but may not appear until 12 hours after exposure (and even later with extended-release formulations). Symptoms can last 24 to 36 hours. Patients who survive 48 hours after acute poisoning are likely to recover. Death may be caused by cardiac arrest due to cardiac cessation or electromechanical dissociation, and in rare cases by ventricular fibrillation. Systemic description of clinical manifestations: Cardiovascular system: Acute: Cardiovascular symptoms are the main feature of quinidine poisoning. Tachycardia caused by anticholinergic effects usually occurs in the early or moderate stages of poisoning. In severe poisoning, bradycardia due to atrioventricular block may occur. Hypotension and shock: Hypotension due to peripheral vasodilation is common. In severe poisoning, cardiogenic shock with elevated central venous pressure, which is associated with decreased myocardial contractility, usually occurs. Cardiac arrest may occur, which may be related to electromechanical dissociation, ventricular arrhythmias, or cardiac cessation. Arrhythmias are common and may include: atrioventricular block, ventricular voluntary rhythms, ventricular tachycardia and ventricular fibrillation, and torsades de pointes. In symptomatic poisoning, ECG changes are consistently present: repolarization abnormalities, T-wave depression, U-wave elevation, QT and PR interval prolongation, QRS complex widening (>0.08 seconds), and atrioventricular block. Syncope due to torsades de pointes may occur. Chronic: ECG changes (including repolarization abnormalities, T-wave depression, and QT interval prolongation) are common features during quinidine treatment. Syncope is associated with transient torsades de pointes, occurring in 1% to 8% of quinidine-treated patients. The occurrence of torsades de pointes is not related to plasma quinidine concentration, but QT interval prolongation increases its likelihood. Respiratory system: Acute: Respiratory depression or apnea is mostly associated with severe cardiac disturbances, such as shock or ventricular arrhythmias. Cases of pulmonary edema with normal pulmonary capillary wedge pressure following suicide attempts have been documented. Nervous System: Central Nervous System: Acute: Drowsiness, delirium, coma, and seizures may occur without cardiac symptoms. However, heart failure should always be considered when central nervous system symptoms are present. Cinchona poisoning may occur occasionally. Chronic: Cinchona poisoning. Delirium has been reported. Peripheral Nervous System: Chronic: Quinidine can enhance the neuromuscular blocking effects of certain skeletal muscle relaxants, and relapse of respiratory paralysis may occur if quinidine is administered shortly after the neuromuscular blockade has been lifted. Autonomic Nervous System: Acute: Quinidine has anticholinergic effects. However, this effect is usually limited to the vagus nerve. Skeletal and Smooth Muscles: Chronic: An elevated serum skeletal muscle enzyme level has been reported in a male patient treated with quinidine. Gastrointestinal Tract: Acute: Nausea and vomiting may occur. Chronic: Gastrointestinal toxicity (nausea, vomiting, diarrhea, and colic) is the most common side effect of quinidine. Liver: Chronic: Hepatotoxicity has been reported, manifested as elevated serum transaminase, lactate dehydrogenase (LDH), and alkaline phosphatase levels, and cholestasis. Kidneys: Acute: No direct nephrotoxicity has been reported. Acute renal failure associated with cardiogenic shock may occur. Skin: Chronic: Skin lesions are associated with quinidine use, including rash, photosensitivity, and lichen planus. Eyes, Ears, Nose, Throat: Local effects: Acute: Cinchona poisoning is rare in acute cases. Toxic doses may cause toxic amblyopia, scotomas, and color vision impairment. Chronic: Long-term cumulative overdose may lead to cinchona poisoning: A patient who took quinidine for two years has been reported to experience headache, tinnitus, dizziness, mydriasis, blurred vision, diplopia, photophobia, deafness, and corneal deposits. Hematologic system: Chronic: Immune thrombocytopenic purpura and hemolytic anemia have been reported. Immune System: Chronic: Quinidine may cause a variety of immune-mediated reactions: thrombocytopenia, hemolytic anemia, angioedema, rash, fever. Metabolism: Acid-Base Imbalance: Acute: Metabolic acidosis may occur in severe poisoning with shock. Fluid and Electrolyte Imbalance: Acute: Hypokalemia is commonly observed. Special Risks: Pregnancy: Chronic: Quinidine doses significantly higher than those required for treating arrhythmias have been shown to cause cranial nerve damage in the fetus. A newborn born to a pregnant woman who took quinidine throughout her pregnancy had the same serum quinidine concentration as the mother. The infant's electrocardiogram was normal, and there was no evidence of teratogenicity. Breastfeeding: Prolonged Breastfeeding: Quinidine concentrations in breast milk are slightly lower than serum concentrations. The dose of quinidine ingested by an infant drinking 1 liter of breast milk is lower than the therapeutic dose. However, breastfeeding is not recommended because quinidine may accumulate in the immature liver of newborns. Identification: Quinidine is a class II antiarrhythmic drug. Source of substance: Quinidine is the D-isomer of quinine. Quinidine is an alkaloid that may be derived from various cinchona species. Quinidine is found in cinchona bark at a concentration of 0.25% to 3.0%. Quinidine can also be prepared from quinine. Quinidine is a powder or white crystal, odorless, and bitter. Quinidine bisulfate is a colorless and odorless crystal with a bitter taste. Quinidine gluconate is a white powder, odorless, and bitter. Quinidine polygalacturonic acid is a powder. Quinidine sulfate is a white powder or odorless crystal with a bitter taste. Indications: Description: Ventricular premature beats and ventricular tachycardia; supraventricular arrhythmias; maintenance of sinus rhythm after cardioversion of atrial fibrillation or atrial flutter. Human exposure: Major risks and target organs: Cardiotoxicity is the major risk of quinidine poisoning. Quinidine may cause central nervous system symptoms. Clinical Overview: Symptoms of poisoning usually appear within 2–4 hours of ingestion, but the timing may vary depending on the quinidine salt and formulation. Symptoms may include cardiac arrhythmias (especially in patients with underlying cardiovascular disease), neurotoxicity, and respiratory depression. Diagnosis: Cardiac disturbances: circulatory arrest, shock, conduction disturbances, ventricular arrhythmias, ECG changes; neurological symptoms: tinnitus, somnolence, syncope, coma, convulsions, delirium; respiratory depression. Quinidine concentration may aid in diagnosis but is not beneficial for clinical treatment. Contraindications: Hypersensitivity or idiosyncratic reaction to cinchona alkaloids; atrioventricular block or complete atrioventricular block; intraventricular block; loss of atrial activity; digitalis poisoning; myasthenia gravis and torsades de pointes. Precautions include: congestive heart failure, hypotension, kidney disease, liver failure; concurrent use of other antiarrhythmic drugs; elderly and lactating women. Route of Administration: Oral: Oral absorption is the most common cause of poisoning. Injection: Poisoning after intravenous administration is rare, but there have been reports of poisoning in patients receiving intravenous quinidine for arrhythmia. Absorption routes: Oral: Quinidine is almost completely absorbed from the gastrointestinal tract. However, due to the first-pass effect in the liver, its absolute bioavailability is approximately 70% to 80% of the ingested dose and may vary depending on the patient and formulation. The time to peak plasma concentration for quinidine sulfate is 1 to 3 hours, for quinidine gluconate it is 3 to 6 hours, and for quinidine polygalacturonic acid it is approximately 6 hours. Sustained-release quinidine can be continuously absorbed over 8 to 12 hours. Parenteral administration: Absorption of quinidine after intramuscular injection can be unstable and unpredictable; the administered dose may not be completely absorbed, possibly due to drug precipitation at the injection site. Other studies have shown no difference in absorption rates between intramuscular and oral quinidine. Distribution by route of administration: Oral: Protein binding: Approximately 70% to 80% of the drug is bound to plasma proteins. Plasma protein binding is reduced in patients with chronic liver disease. Tissues: Quinidine concentrations in the liver are 10 to 30 times higher than in plasma. Quinidine levels in skeletal muscle, cardiac muscle, brain, and other tissues fall between these concentrations. The erythrocyte-plasma partition ratio is 0.82. Biological half-life (by route of exposure): Elimination half-life: The half-life is approximately 6 to 7 hours. The elimination half-life is prolonged in chronic liver disease and in the elderly. Congestive heart failure or renal failure does not appear to alter its elimination half-life. Metabolism: 50% to 90% of quinidine is metabolized in the liver to hydroxylated products. Metabolites include 3-hydroxyquinidine, 2-oxoquinidine, O-demethylquinidine, and quinidine-N-oxide. The major metabolite is 3-hydroxyquinidine, which has similar effects to quinidine and may partially explain the observed antiarrhythmic effects. The elimination kinetics of hydroxyquinidine appear to be similar to those of quinidine. Excretion: Renal: The amount excreted unchanged in the urine varies from person to person, but is approximately 17% of the administered dose. Up to 50% of quinidine (original form + metabolites) is excreted in the urine within 24 hours after administration. Renal excretion depends on urine pH. Excretion is inversely proportional to urine pH. Renal insufficiency and congestive heart failure reduce excretion. Liver: 50% to 90% of quinidine is metabolized in the liver. Bile: Approximately 1% to 3% of quinidine is excreted in feces via bile. Breast milk: Quinidine is secreted into breast milk. Mechanism of action: Toxicology: Quinidine reduces myocardial permeability to electrolytes (membrane stabilizer) and is a systemic cardiac depressant. It has negative inotropic effects; inhibits spontaneous diastolic depolarization; slows conduction velocity; quinidine can prolong the effective refractory period and increase the electrical threshold. This leads to decreased myocardial contractility, impaired conduction (atrioventricular and intraventricular conduction), and reduced excitability, but may be accompanied by anomalous reentry mechanisms. Quinidine has anticholinergic and peripheral vasodilatory effects. In experimental studies, the following progressive changes were observed: Electrocardiogram: bradycardia, prolonged PR interval, prolonged QT interval, widened QRS complex, and the appearance of ventricular voluntary rhythm, eventually developing into ventricular arrest. Sometimes, the terminal event is ventricular fibrillation. Blood pressure gradually decreases. Blood pressure drops significantly when QRS complex widening occurs, and approaches zero when slow ventricular voluntary rhythm occurs. Electrolyte disturbances: decreased plasma potassium, sodium, and magnesium concentrations, and acidosis. Electrolytes: hypokalemia may occur, possibly related to quinidine's direct effect on cell membrane permeability, leading to intracellular potassium ion transport. Neurological symptoms: Syncope and seizures may represent direct toxicity to the central nervous system or may be associated with cerebral ischemia due to circulatory or respiratory failure. Pharmacodynamics: Quinidine slows the firing rate of normal and ectopic pacemakers; increases the threshold for electrically induced arrhythmias; prevents ventricular arrhythmias; and may prevent or terminate vortex fibrillation. Teratogenicity: Quinidine has been shown to cause minor cranial nerve damage in fetuses, even at doses far exceeding those required for the treatment of arrhythmias. Drug interactions: Several drug interactions have been reported. Quinidine has a synergistic effect with warfarin (lowering prothrombin levels). Quinidine can enhance the effects of both non-depolarizing and depolarizing neuromuscular blocking agents. The cardiac depressant effect of quinidine is enhanced when used in combination with other antiarrhythmic drugs; amiodarone can increase the concentration of quinidine in the blood. Rifampin, anticonvulsants, nifedipine, and acetazolamide can decrease the concentration of quinidine. Antacids, cimetidine, verapamil, and amiodarone can increase quinidine concentrations; terfenadine, astemizole, thiazide diuretics, and loop diuretics increase the risk of quinidine poisoning. Quinidine can increase plasma concentrations of propafenone and digoxin. Major adverse reactions: Various adverse reactions have been reported during quinidine treatment. Cardiovascular system: Hypotension; syncope; arrhythmia: Torsades de pointes; ECG: QRS widening, PR and QT interval prolongation. Central nervous system: Cinchona poisoning: headache, fever, visual disturbances, mydriasis, tinnitus, nausea, vomiting, and rash. Gastrointestinal system: Nausea, vomiting, diarrhea, and colic have been reported. Hepatology: Granulomatous hepatitis or hepatitis with centrilobular necrosis. Skin: Drug fever and photosensitive rash may occur. Hematologic system: Thrombocytopenia (immune reaction) has been reported. Clinical Manifestations: Acute Poisoning: Ingestion: The severity of quinidine poisoning is related to cardiotoxicity. Symptoms usually appear within 2 to 4 hours and may include: Cardiovascular symptoms: hypotension, cardiogenic shock, cardiac arrest. Electrocardiogram may show: decreased T waves; prolonged QT and QRS intervals; atrioventricular block; ventricular arrhythmias (torsades de pointes). Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsions, blurred vision, and diplopia. Respiratory symptoms: hypoventilation and apnea. Cardiotoxicity may be enhanced if other cardiotoxic drugs (antiarrhythmic drugs, tricyclic antidepressants) are ingested concurrently. Parenteral exposure: Symptoms appear more quickly after intravenous administration. Chronic Poisoning: Ingestion: The most relevant symptoms of chronic poisoning are: electrocardiographic abnormalities; syncope due to ventricular arrhythmias (torsades de pointes) and cinchona poisoning; gastrointestinal disturbances. Course, prognosis, and cause of death: The typical course of quinidine poisoning is characterized by cardiovascular disturbances, usually appearing within the first 2 to 4 hours, but may not appear until 12 hours after exposure (even later with sustained-release formulations). Symptoms can last 24 to 36 hours. Patients who survive 48 hours after acute poisoning usually recover. Death may be caused by cardiac arrest due to cardiac cessation or electromechanical dissociation, and in rare cases by ventricular fibrillation. Systemic description of clinical manifestations: Cardiovascular system: Acute: Cardiovascular symptoms are the main feature of quinidine poisoning. Tachycardia caused by anticholinergic effects usually occurs in the early or moderate stages of poisoning. In severe poisoning, bradycardia due to atrioventricular block may occur. Hypotension and shock: Hypotension due to peripheral vasodilation is common. In severe poisoning, cardiogenic shock with elevated central venous pressure, associated with decreased myocardial contractility, usually occurs. Cardiac arrest may occur, possibly related to electromechanical dissociation, ventricular arrhythmias, or cardiac cessation. Cardiac arrhythmias are common and may include: atrioventricular block, voluntary ventricular rhythms, ventricular tachycardia and ventricular fibrillation, and torsades de pointes. In symptomatic poisoning, ECG changes are consistently present: repolarization abnormalities, T-wave depression, U-wave elevation, QT and PR interval prolongation, QRS complex widening (>0.08 seconds), and atrioventricular block. Torsades de pointes can cause syncope. Chronic poisoning: ECG changes (including repolarization abnormalities, T-wave depression, and QT interval prolongation) are common features during quinidine treatment. Syncope is associated with transient torsades de pointes, occurring in 1% to 8% of patients receiving quinidine. The occurrence of torsades de pointes is not related to plasma quinidine concentration, but QT interval prolongation increases its likelihood. Respiratory system: Acute: Respiratory depression or apnea is mostly associated with severe cardiac disturbances such as shock or ventricular arrhythmias. Literature has documented cases of pulmonary edema following suicide attempts, despite normal pulmonary capillary wedge pressure. Nervous System: Central Nervous System: Acute: Drowsiness, delirium, coma, and seizures may occur without cardiac symptoms. However, heart failure should always be considered when central nervous system symptoms are present. Cinchona poisoning may occur occasionally. Chronic: Cinchona poisoning. Delirium has been reported. Peripheral Nervous System: Chronic: Quinidine can enhance the neuromuscular blocking effects of certain skeletal muscle relaxants; if quinidine is administered shortly after the neuromuscular blockade has been lifted, it may lead to a relapse of respiratory paralysis. Autonomic Nervous System: Acute: Quinidine has anticholinergic effects. However, this effect is usually limited to the vagus nerve. Skeletal and Smooth Muscle: Chronic: An elevated serum skeletal muscle enzyme concentration has been reported in a male patient treated with quinidine. Gastrointestinal Tract: Acute: Nausea and vomiting may occur. Chronic: Gastrointestinal toxicity (nausea, vomiting, diarrhea, and colic) is the most common side effect of quinidine. Liver: Chronic: Hepatotoxicity has been reported, manifested as elevated serum transaminase, lactate dehydrogenase (LDH), and alkaline phosphatase levels, and cholestasis. Kidneys: Acute: No direct nephrotoxicity has been reported. Acute renal failure associated with cardiogenic shock may occur. Skin: Chronic: Skin lesions, including rash, photosensitivity, and lichen planus, have been reported with quinidine. Eyes, Ears, Nose, Throat: Local Reactions: Acute: Cinchona poisoning is rare in acute poisoning. Toxic doses can cause toxic amblyopia, scotomas, and color vision impairment. Chronic: Long-term cumulative overdose can cause cinchona poisoning: A patient who took quinidine for two years has been reported to experience headache, tinnitus, dizziness, mydriasis, blurred vision, diplopia, photophobia, deafness, and corneal deposits. Hematologic System: Chronic: Quinidine has been reported to cause immune thrombocytopenic purpura and hemolytic anemia. Immune System: Chronic: Quinidine can cause a variety of immune-mediated reactions: thrombocytopenia, hemolytic anemia, angioedema, rash, fever. Metabolism: Acid-Base Imbalance: Acute: Metabolic acidosis can occur in severe poisoning with shock. Fluid and Electrolyte Imbalance: Acute: Hypokalemia is common. Special Risks: Pregnancy: Long-term: Quinidine has been shown to cause cranial nerve damage in the fetus, even at doses far higher than those required to treat arrhythmias. A newborn born to a pregnant woman who took quinidine throughout her pregnancy had the same serum quinidine concentration as the mother. The infant's electrocardiogram was normal, and there was no evidence of teratogenicity. Lactation: Long-term: Quinidine is present in breast milk, but at slightly lower concentrations than in serum. The amount of quinidine ingested by an infant in 1 liter of breast milk is lower than the therapeutic dose. However, breastfeeding is not recommended because quinidine can accumulate in the immature liver of newborns. /Quinidine/

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Hepatotoxicity
Long-term use of quinidine is associated with a lower incidence of elevated serum enzymes, which are usually mild, asymptomatic, and resolve spontaneously even without dose changes. In addition, there have been numerous reports of acute hypersensitivity reactions (including liver involvement) caused by quinidine. These reactions usually occur 1 to 2 weeks after treatment, but may also occur within 24 hours of restarting or resuming quinidine use. Clinical manifestations include fatigue, nausea, vomiting, diffuse muscle aches, arthralgia, and high fever. Early blood tests show elevated serum transaminase and alkaline phosphatase levels, as well as mild jaundice, which may persist for several days and worsen even after discontinuation of quinidine. The pattern of elevated serum enzymes is usually cholestatic or mixed. Skin rash is uncommon, and eosinophilia is also atypical, despite the presence of other signs of hypersensitivity (fever, arthralgia). Autoantibodies are usually undetectable. Liver biopsies typically show mild damage and small epithelioid granulomas, which are common in many organs in systemic hypersensitivity reactions. Quinine (an optical isomer of quinidine, primarily used as an antimalarial drug) can also cause similar clinical presentations of liver injury. Reports of quinidine-induced liver injury are rare in recent years, possibly because quinidine is now rarely used. Probability Score: A (Etiology of clinically confirmed liver injury). Effects during pregnancy and lactation. ◉ Overview of use during lactation: Limited information suggests that with mothers taking no more than 1.8 grams of quinidine daily, the concentration of quinidine in breast milk is very low and is not expected to have any adverse effects on breastfed infants, especially if the infant is older than 2 months. If a breastfeeding woman uses this drug, the exclusively breastfed infant should be closely monitored, and serum drug concentrations may need to be measured to rule out toxicity if there are any concerns. ◉ Effects on breastfed infants: As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding
At concentrations of 6.5 to 16.2 µmol/L, 80% to 88% of quinidine is bound to plasma proteins, primarily α1-acid glycoprotein and albumin. This percentage is lower in pregnant women and may be as low as 50% to 70% in infants and newborns.

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Interactions
The combined use of propranolol and quinidine enhances β-receptor blocking, manifested as decreased exercise heart rate and prolonged QTc and PR intervals…Quinidine stereoselectively inhibits propranolol metabolism by inhibiting dehydroisovaleric acid isoenzymes. Quinidine leads to increased propranolol concentrations, thereby enhancing β-receptor blocking.
Ethanoic acid and furosemide (diuretics) can increase the lipid solubility and renal tubular reabsorption of quinidine, thus prolonging its therape

[1]. Quinidine. [Updated 2023 Aug 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

Therapeutic Uses
Quinidine is indicated for the treatment of recurrent, documented, life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Quinidine should not be used to treat milder ventricular arrhythmias, such as asymptomatic premature ventricular contractions. /US Product Label Includes/ Quinidine is indicated for the treatment of symptomatic atrial fibrillation or atrial flutter, especially in patients whose symptoms cannot be controlled by measures to lower the ventricular rate. /US Product Label/ Chronic quinidine treatment is recommended for certain patients at high risk of symptomatic atrial fibrillation or atrial flutter, such as those with a history of frequent episodes and poor tolerance, for whom prophylactic quinidine treatment is too risky. /US Product Label/ Intravenous quinidine is indicated for the treatment of life-threatening Plasmodium falciparum malaria. /US Product Label/
Veterinary Drug: Among the six antiarrhythmic drugs tested, quinidine sulfate showed no protective effect against canine-induced arrhythmias.
…It is effective for the short-term and long-term treatment of supraventricular and ventricular arrhythmias. Quinidine
In fact, quinidine is usually administered orally only, but in special cases it can also be administered intramuscularly or intravenously. The usual oral dose of quinidine sulfate is 200 to 300 mg three to four times daily. …It is suitable for patients with atrial or ventricular premature beats or for maintenance therapy. For the treatment of paroxysmal ventricular tachycardia, higher doses and/or more frequent administration may be used in the short term.
Quinidine is primarily used for prophylactic treatment to maintain normal sinus rhythm restored after conversion of atrial fibrillation and/or atrial flutter by other methods. This drug is also used to prevent the recurrence of paroxysmal atrial fibrillation, paroxysmal atrial tachycardia, paroxysmal atrioventricular junctional rhythm, paroxysmal ventricular tachycardia, and atrial or ventricular premature beats.
For more complete data on the therapeutic uses of quinidine sulfate (7 types), please visit the HSDB record page.

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Drug Warnings
Skin reactions to quinidine are rare, including measles-like and scarlet fever-like rashes, urticaria, rash, pruritus, exfoliative dermatitis, eczema, severe exacerbation of psoriasis, lichenification, flushing, pigmentary abnormalities, photosensitive dermatitis, and contact dermatitis.
...Adverse reactions are not related to plasma concentrations and include drug fever and cholestatic cholestasis. Hepatitis, systemic lupus erythematosus, asthma, allergic reactions, thrombocytopenia, hemolytic anemia (especially in glucose-6-phosphate dehydrogenase deficiency), and hypoprothrombinemia. Skin changes include maculopapular rash, thrombocytopenic purpura, cutaneous vasculitis, photosensitivity, and bullous lesions.
Drug-induced agranulocytosis is a clinical condition characterized by a selective reduction in circulating neutrophils, typically decreasing to below 0.2 × 10⁹/L after drug administration. Quinidine is a widely used antiarrhythmic drug in outpatient settings with some known hematological side effects. Mid-term use of quinidine has been associated with a small number of cases of agranulocytosis. This article describes a case of a 60-year-old male patient with atrial fibrillation who developed sudden agranulocytosis 3 days after taking quinidine; neutrophil levels returned to normal on the third day of hospitalization.
High doses…increase the time dispersion of the ventricular refractory period…may induce ventricular spontaneous impulses. Caution…when used…caution must be exercised when treating ventricular ectopic rhythms; increasing the dose after treatment failure may increase the risk.
For more complete data on drug warnings for quinidine (34 in total), please visit the HSDB record page.
Syndrome or sudden death has occasionally occurred in patients taking quinidine…possibly due to excessively high plasma quinidine concentrations or concurrent digitalis toxicity. Quinidine
Patients with long QT syndrome or those whose QT interval is significantly prolonged in response to low-concentration quinidine treatment appear to be particularly prone to syncope or sudden death and should not be treated with this drug.
High plasma concentrations of quinidine can cause adverse reactions in any patient. Due to the low treatment rate of quinidine, close monitoring is required for every patient taking this drug.
Quinidine should be used with extreme caution, or even avoided altogether, in patients with incomplete atrioventricular block, as it may lead to complete atrioventricular block and cardiac arrest. Intramuscular or intravenous administration of quinidine is particularly dangerous in patients with atrioventricular block, absence of atrial activity, and extensive myocardial damage. For patients requiring high-dose antiarrhythmic drugs to control ventricular arrhythmias, enhancing factors such as hypokalemia, hypoxia, and acid-base imbalances must be eliminated.
For more complete data on drug warnings for quinidine sulfate (24 in total), please visit the HSDB record page.

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Pharmacodynamics
Quinidine is an antimalarial schizotoxic agent and a class Ia antiarrhythmic drug used to interrupt or prevent reentrant arrhythmias and arrhythmias caused by increased automaticity, such as atrial flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia. In most patients, quinidine causes an increase in sinus heart rate. Quinidine can significantly prolong the QT interval in a dose-dependent manner, acting as an alpha-adrenergic antagonist with anticholinergic and negative inotropic effects. Quinidine-induced QT interval prolongation can lead to increased ventricular automaticity and polymorphic ventricular tachycardia, such as torsades de pointes. Bradycardia, hypokalemia, hypomagnesemia, or high serum quinidine concentrations increase the risk of torsades de pointes. However, this arrhythmia can occur even in the absence of any of these factors. Patients receiving quinidine may also experience paradoxical increases in ventricular rate during atrial flutter/fibrillation, while patients with sick sinus syndrome receiving quinidine may experience significant sinus node suppression and bradycardia.

C20H24N2O2

324.4168

324.183

C, 74.04; H, 7.46; N, 8.64; O, 9.86

56-54-2

Quinidine hydrochloride monohydrate;6151-40-2;Quinidine sulfate;50-54-4;Quinidine sulfate dihydrate;6591-63-5;Quinidine polygalacturonate;27555-34-6;Quinidine gluconic acid;7054-25-3;Quinidine-d3;1267657-68-0; 747-45-5 (bisulfate); 56-54-2; 1668-99-1 (HCl);

441074

CRYSTALS WITH 2.5 MOL WATER OF CRYSTALLIZATION; CRYSTALS FROM DILUTE ALCOHOL
Occurs as fine, needle-like, white crystals which frequently cohere in masses or as a fine, white powder.

1.2±0.1 g/cm3

495.9±40.0 °C at 760 mmHg

168-172 °C(lit.)

253.7±27.3 °C

0.0±1.3 mmHg at 25°C

1.638

3.44

1

4

4

24

457

4

O([H])[C@@]([H])(C1C([H])=C([H])N=C2C([H])=C([H])C(=C([H])C=12)OC([H])([H])[H])[C@@]1([H])C([H])([H])C2([H])C([H])([H])C([H])([H])N1C([H])([H])[C@]2([H])C([H])=C([H])[H]

LOUPRKONTZGTKE-LHHVKLHASA-N

InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14-,19+,20-/m0/s1

(S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol

(+)-Quinidine; Conquinine; Pitayine; Chinidin; Conchinin; (8R,9S)-Quinidine;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~154.12 mM)
Ethanol : ~14.29 mg/mL (~44.05 mM)
H2O : ~0.67 mg/mL (~2.07 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)